COX2-dependent suppression of anticancer immunity.

Prostaglandin E2 (PGE2) is well known to promote tumor progression by boosting cancer cell proliferation while inhibiting anticancer immunity. Recent data from Lacher et al. and Morotti et al. demonstrate that one of the mechanisms through which PGE2 suppresses tumor-targeting immune responses involves downregulation of interleukin 2 (IL2) receptors and consequent inhibition of mitochondrial metabolism in T cells.

Dispositional greed and life satisfaction: the role of social comparison for well-being.

There is a lack of studies addressing the psychological mechanisms underlying the association between individual differences in greed and well-being. This study tested the relationship between dispositional greed, and satisfaction with life, as well as the moderating effect of social comparison orientation on this association (N = 373). As expected for hypothesis 1, we found that greed correlated negatively with satisfaction with life, and positively with social comparison orientation, even after controlling for individuals' mental health index (anxiety and depression), supporting the hypothesis 2. Further, the moderating effect of social comparison strengthened the relationship between high levels of dispositional greed and dissatisfaction with life, failing to support hypothesis 3. As such, individuals high on dispositional greed were less satisfied with life if they also showed lower (vs. medium level) levels of social comparison orientation. These findings add to the psychological literature on greed by showing that social comparison is not only positively related to it but can also be a vital mechanism for boosting psychological well-being.

Adaptive inhibition of CGAS signaling by TREX1.

Mammalian cells react to the accumulation of double-stranded (ds)DNA in the cytosol by secreting antiviral and proinflammatory cytokines, notably type I interferon (IFN). Recent data reported by Tani et al. demonstrate that overactivation of this pathway is prevented by an adaptive feedback mechanism elicited by type I IFN receptors and executed by the exonuclease three prime repair exonuclease 1 (TREX1).

Evaluation of the Chilean National Orthopaedic Examination Over 11 Years: Progress and Outcomes of National and International Examinees.

INTRODUCTION: The National Orthopaedics Examination (EMNOT) was initially designed for Chilean orthopaedic program graduates and is now a crucial component of the revalidation process for international orthopaedic surgeons seeking practice in Chile. This study aims to describe participation and performance of EMNOT examinees based on their origin and to analyze the difficulty and discrimination indexes during its first 11 years of implementation. METHODS: A retrospective assessment was conducted on all EMNOT results from 2009 to 2019. The study evaluated the participation and performance of examinees according to their origin and examined the difficulty and discrimination indexes of the examination. RESULTS: A total of 975 examinees were evaluated, with 41.23% from national resident programs (National Medical Graduates) and 58.77% from international examinees (International Medical Graduates). The number of participating universities increased from 4 in 2009 to 17 in 2019. National Medical Graduates examinees achieved a mean score of 66.52 ± 8.67 (0 to 100 points) while International Medical Graduates examinees scored 55.13 ± 11.42 (P < 0.001). The difficulty and discrimination indexes remained adequate throughout this period. DISCUSSION: Over the course of 11 years, the number of EMNOT examinees exhibited notable growth. The examination effectively differentiates between candidates based on their origin and maintains appropriate levels of difficulty and discrimination.

Tibial tubercle to trochlear groove and the roman arch method for tibial tubercle lateralisation are reliable and distinguish between subjects with and without major patellar instability.

PURPOSE: Patellofemoral (PF) instability recurrence depends on several factors including the relative lateralisation of tibial tubercle (TT) regarding the trochlear groove (TG). TT relative lateralisation quantification has long been a topic of debate. Multiple measuring techniques have been described including TT-trochlear groove (TT-TG), TT-posterior cruciate ligament (TT-PCL) and TT-roman arch (TT-RA), with no clear consensus regarding the most reliable index or pathologic threshold. We set out to determine the normal value range of each index and their association with age, sex and PF instability status. Also, this study aims to determine a reliable pathologic distance threshold to effectively predict patellar dislocation. METHODS: Skeletally mature patients up to 45 years of age who presented a CT Scan and an MRI of the same knee between 2014 and 2018 were included and divided into subgroups based on history of PF instability. Three indexes (TT-TG, TT-PCL and TT-RA) were assessed by two independent observers blinded to instability history. ROC curves were performed for each index to obtain the cut point that better predicts instability. Univariate and multivariate models adjusted by age, sex, instability history and type of imaging technique were performed to test the influence of these variables. RESULTS: 208 patients were included. Mean age was 27.93 â€‹± â€‹8.48 years, 67.3% were female and 71 patients (34.1%) presented major instability history. Good or excellent inter and intraobserver reliability was found for all three indexes. All indexes presented significantly different distributions between subjects with and without major instability (p â€‹< â€‹0.001), except for TT-PCL. Different cut point values differing between imaging modalities were found: 11.4 â€‹mm for MRI TT-TG, 17 â€‹mm for CT TT-TG, 15.6 â€‹mm for MRI TT-RA and 18.2 â€‹mm for CT TT-RA. CONCLUSIONS: All indexes studied had good or excellent inter and intraobserver reliability. Measurements between imaging techniques (CT and MR) are not interchangeable. Both TT-TG and TT-RA correctly distinguish between subjects with and without major instability, while TT-PCL does not, recommending caution when evaluated on its own. Specific threshold values depending on imaging technique should be considered for surgical decision-making. LEVEL OF EVIDENCE: Level IV, Diagnostic Test.

Preoperative education in patients undergoing foot and ankle surgery: a scoping review.

BACKGROUND: International guidelines promote preoperative education for patients undergoing orthopedic surgery. However, the evidence sustaining these recommendations comes mainly from studies for hip and knee replacement surgery. Little is known about patients undergoing foot and ankle surgery. We aimed to map and characterize all the available evidence on preoperative education for patients undergoing foot and ankle surgery. METHODS: This study complies with the PRISMA-ScR guidelines. We searched eight databases, including MEDLINE, Embase, and CENTRAL. We performed cross-citations and revised the references of included studies. We included studies addressing preoperative education in patients undergoing foot and ankle surgery. We did not exclude studies because of the way of delivering education, the agent that provided it, or the content of the preoperative education addressed in the study. Two independent authors screened the articles and extracted the data. The aggregated data are presented in descriptive tables. RESULTS: Of 1596 retrieved records, only 15 fulfilled the inclusion criteria. Four addressed preoperative education on patients undergoing foot and ankle surgery and the remaining 11 addressed a broader population, including patients undergoing foot and ankle surgery but did not provide separate data of them. Two studies reported that preoperative education decreases the length of stay of these patients, another reported that education increased the knowledge of the participants, and the other leaflets were well received by patients. CONCLUSION: This scoping review demonstrates that evidence on preoperative education in foot and ankle surgery is scarce. The available evidence supports the implementation of preoperative education in patients undergoing foot and ankle surgery for now. The best method of education and the real impact of this education remain to be determined.

Desarrollo e implementación de un programa de investigación durante la residencia de ortopedia y traumatología / Development and implementation of a research program during the orthopedics residency

Introducción: Dentro de las recomendaciones internacionales para la formación de médicos expertos, se encuentra el integrar la mejor evidencia disponible a la práctica clínica y contribuir a la creación del conocimiento científico. El objetivo de este trabajo es describir la implementación de un programa formal de investigación en residentes de ortopedia y traumatología. Metodología: Se desarrolló un programa de investigación para residentes de ortopedia y traumatología, coordinado por un equipo con formación en metodología y bioestadística. El objetivo principal fue que los residentes lograran adquirir herramientas en el desarrollo del método científico e integrar la medicina basada en la evidencia en la práctica profesional. Para ello, se enfocó en tres ejes: 1. formación general 2. análisis crítico de la literatura y 3. desarrollo de investigación científica. Resultados: El año 2015 se implementó el programa. Comenzó con el módulo de formación general a través de seminarios de investigación y una rotación mensual obligatoria. De forma semanal se implementaron reuniones de revisiones críticas de la literatura a partir de casos clínicos y cada dos o tres meses sesiones de journal club. Se han formulado 30 proyectos de investigación, 22 de ellos se han presentado en congresos y ha habido un total de 27 publicaciones con coautoría de residentes (6 de primer autor). Conclusión: A través del programa de investigación, los residentes han adquirido herramientas para poder integrar la medicina basada en la evidencia a su práctica profesional y desarrollar proyectos científicos.

Introduction: In the international recommendations for resident education, there is integrating the best available evidence into clinical practice and contributing to the creation of scientific knowledge. This research aims to describe implementing a formal research program for orthopedic residents. Methodology: We developed a research program for orthopedic residents coordinated by a team trained in methodology and biostatistics. The main objective for residents was to acquire tools to develop the scientific method and to integrate evidence-based medicine into professional practice. To do this, it focused on: 1. theoretical courses, 2. critical analysis of literature, and 3. creation of scientific research. Results: 2015, the program started with a theoretical course through research seminars and a mandatory monthly rotation. Critical analysis of articles meetings were weekly, and journal club sessions every 2 or 3 months. Residents formulated 30 research projects and presented 22 at national and international congresses. There were 27 scientific publications with resident participation (6 were lead authors). Conclusion: Through the research program, residents have acquired tools to integrate evidence-based medicine into their professional practice and develop scientific projects.

Toxicological safety, antioxidant activity and phytochemical characterization of leaf and bark aqueous extracts of Commiphora leptophloeos (Mart.) J.B. Gillett.

This study aimed to characterize the phytochemical profile of bark and leaves aqueous extract Commiphora leptophloeos, and conduct in vivo and in vitro assays to determine the presence of any toxicological consequences due to exposure. The phytochemical analysis was carried out using high-performance liquid chromatography (HPLC). The antioxidant activity was estimated utilizing DPPH free radical scavenging and phosphomolybdenum assays. Cell viability was measured by the MTT method on J774 and human adenocarcinoma cells, which were treated with concentrations of 12,5, 25, 50, 100 or 200 µg/ml of both extracts. Acute oral toxicity, genotoxicity, and mutagenicity assays were determined using a single oral dose of 2000 g/kg in male Swiss albino mice (Mus musculus). Biochemical analysis of the blood and histological analyses of the kidneys, liver, spleen, pylorus, duodenum and jejunum were undertaken. Genotoxicity and mutagenicity were determined utilizing blood samples. Gallic acid, catechin, and epicatechin were identified in the bark and chlorogenic acid in leaves. Data demonstrated a high content of phenolic compounds and flavonoids associated with significant antioxidant potential. No significant signs in damage or symptoms of toxicity were detected. No marked reduction in cell viability was found at lower concentrations tested. On histomorphometry, only the gastrointestinal organs exhibited significant difference. Renal hepatic and blood parameters were within the normal range. No apparent signs of toxicity, genotoxicity, mutagenicity or cytotoxicity were found in vivo and in vitro experiments.

Educación en pacientes adultos mayores sometidos a endoprótesis total de cadera: Un enfoque centrado en las preferencias de los pacientes / Education in older patients undergoing total hip endoprosthesis: An approach focused on patient preferences

Propósito del estudio: Explorar las preferencias educativas de los beneficiarios adultos de las Garantías Explicitas en Salud (GES) sometidos a una cirugía de endoprótesis total de cadera. Material y método: Estudio descriptivo de carácter mixto. Se diseñó una encuesta que exploró las preferencias educativas referentes a cada etapa del proceso quirúrgico de adultos mayores sometidos electivamente a endoprótesis total de cadera en un centro hospitalario universitario. La encuesta se aplicó retrospectivamente de manera telefónica por un encuestador entrenado. El tiempo transcurrido entre la aplicación de la encuesta y la cirugía fue entre 2 y 14 meses. Resultados: Se incluyeron 63 pacientes, cuya edad promedio fue 72,5 años y el 69,8% correspondía al sexo femenino. Con respecto a su previsión de salud el 57,2% era beneficiario de FONASA y el 42,7% de ISAPRE. Las preferencias de información descritas en nuestra muestra con respecto al proceso quirúrgico desde su inicio a fin, señalan a la cirugía propiamente tal (40,4%) y los cuidados post operatorios (29,3%) como los temas de más interés. Los temas de menor interés fueron los relacionados con cuidados preoperatorios (45,2%) y al proceso de hospitalización (31,7%). Los pacientes encuestados valoraron la información entregada previa a su cirugía como adecuada, útil y fácil de entender. Conclusiones: Los adultos mayores sometidos a endoprótesis señalaron la información específica referente a la cirugía y los cuidados post operatorios como los temas educativos de mayor interés. La información estándar entregada por los médicos tratantes fue bien recibida por los pacientes.

Purpose of the study: To explore the educational preferences of adults aged 65 years and older with hip osteoarthritis undergoing total hip replacement (THA). Methods: Mixed descriptive study. A survey was designed to explore the educational preferences regarding each stage of the surgical process in elderly patients undergoing electively THA for osteoarthritis in a university-affiliated hospital. The survey was applied retrospectively and telephonically by a trained interviewer between 2 and 14 months after the surgery.Results: Sixty-three patients were surveyed, whose average age was 72.5 years, and 69.8% corresponded to females. Regarding their health coverage, 57.2% were beneficiaries of FONASA and 42.7% of ISAPRE. The educational preferences described in our sample regarding the surgical process from its beginning to the end indicate that surgery (40.4%) and post-operative care (29.3%) as the most relevant topics. The topics of least interest were preoperative care (45.2%) and information related to hospitalization (31.7%). The surveyed pa-tients rated their treating physician's education as adequate, helpful, and easy to understand before their surgery. Conclusions: Elderly patients undergoing THA indicated that specific surgery and post-operative care information are the most relevant educational topics.

Histological evaluation of the liver of mice with sarcoma-180 treated with salazinic acid.

Many of the drugs used to fight cancer cells induce various damage causing hepatotoxic effects which are characterized by tissue changes. The aim of the study is to know the possible effects of salazinic acid on livers of mice exposed to Sacoma-180. The tumor was grown in the animals in ascitic form and inoculated subcutaneously in the axillary region of the mouse developing the solid tumor. Treatment with salazinic acid (25 and 50 mg/kg) and 5-Fluorouracil (20 mg/kg) started 24-hours after inoculation and was performed for 7 days. To verify these effects, the qualitative method of histological criteria investigated in liver tissue was used. It was observed that all treated groups showed an increase of pyknotic nuclei in relation to the negative control. There was an increase in steatosis in all groups compared to the negative control but there was a decrease in the groups treated with salazinic acid in the 5-Fluorouracil. There was no necrosis in the salazinic acid treated groups. However, this effect was seen in 20% of the positive control group. Therefore, it can be concluded that salazinic acid did not show hepatoprotective action on mice but demonstrated a decrease in steatosis and absence of tissue necrosis.

NCoA3 upregulation in breast cancer­associated adipocytes elicits an inflammatory profile.

Nuclear receptor coactivator 3 (NCoA3) is a transcriptional coactivator of NF­κB and other factors, which is expressed at relatively low levels in normal cells and is amplified or overexpressed in several types of cancer, including breast tumors. NCoA3 levels have been shown to be decreased during adipogenesis; however, its role in tumor­surrounding adipose tissue (AT) remains unknown. Therefore, the present study assessed the modulation of NCoA3 in breast cancer­associated adipocytes and evaluated its association with the expression of inflammatory markers. 3T3­L1 adipocytes were stimulated with conditioned medium from human breast cancer cell lines and the expression levels of NCoA3 were evaluated by reverse transcription­quantitative (q)PCR. NF­κB activation was measured by immunofluorescence, and tumor necrosis factor and monocyte chemoattractant protein 1 levels were analyzed by qPCR and dot blot assays. The results obtained from the in vitro model were supported using mammary AT (MAT) from female mice, MAT adjacent to tumors from patients with breast cancer and bioinformatics analysis. The results revealed that adipocytes expressing high levels of NCoA3 were mainly associated with a pro­inflammatory profile. In 3T3­L1 adipocytes, NCoA3 downregulation or NF­κB inhibition reversed the expression of inflammatory molecules. In addition, MAT from patients with a worse prognosis exhibited high levels of this coactivator. Notably, adipocyte NCoA3 levels could be modulated by inflammatory signals from tumors. The modulation of NCoA3 levels in synergy with NF­κB activity in MAT in a tumor context could be factors required to establish breast cancer­associated inflammation. As adipocytes are involved in the development and progression of breast cancer, this signaling network deserves to be further investigated to improve future tumor treatments.

Assessment of Cytotoxic/Antitumour Potential and in silico Study of Salazinic Acid Isolated from Parmotrema concurrens.

INTRODUCTION: Despite numerous scientific advances, cancer continues to be one of the main causes of death in the world. This situation has driven the search for promising molecules. Lichen substances have been widely described for their pharmacological potential. OBJECTIVE: The present study evaluated the antitumour potential of a depsidone isolated from Parmotrema concurrens- salazinic acid (SAL) - through in vitro, in vivo and in silico studies. METHODS: The molecule was isolated from the acetonic extract of the lichen and recrystallized in acetone. The macrophage J774, sarcoma-180 and MDA-MB-231 cell lines were used for the MTT cytotoxicity assay. The antitumor assay used a murine model (Swiss albino mice) with sarcoma-180. The animals were treated for seven consecutive days with doses of SAL (25 and 50 mg/kg) and 5-fluorouracil (20 mg/kg). RESULTS: Its purity was determined using high-performance liquid chromatography (94%), and its structure was confirmed by H1 and C13 nuclear magnetic resonance. SAL was not considered toxic to cancer cell lines, showing cell viability rates of 79.49 ± 4.15% and 86.88 ± 1.02% for sarcoma-180 and MDA-MB-231, respectively. The tumour inhibition rate was greater than 80% in the animals treated with SAL and 65% for those that received 5-fluorouracil. Simulations of molecular dynamics to estimate the flexibility of the interactions between human thymidylate synthase and derivatives of SAL and 5-fluorouracil revealed that SAL exhibited greater enzymatic interaction capacity, with highly favourable energy, compared to 5-fluorouracil. CONCLUSION: The present results demonstrate the potential of salazinic acid as a tumour inhibition agent.

Immunological mechanisms involved in macrophage activation and polarization in schistosomiasis.

Human schistosomiasis is caused by helminths of the genus Schistosoma. Macrophages play a crucial role in the immune regulation of this disease. These cells acquire different phenotypes depending on the type of stimulus they receive. M1 macrophages can be 'classically activated' and can display a proinflammatory phenotype. M2 or 'alternatively activated' macrophages are considered anti-inflammatory cells. Despite the relevance of macrophages in controlling infections, the role of the functional types of these cells in schistosomiasis is unclear. This review highlights different molecules and/or macrophage activation and polarization pathways during Schistosoma mansoni and Schistosoma japonicum infection. This review is based on original and review articles obtained through searches in major databases, including Scopus, Google Scholar, ACS, PubMed, Wiley, Scielo, Web of Science, LILACS and ScienceDirect. Our findings emphasize the importance of S. mansoni and S. japonicum antigens in macrophage polarization, as they exert immunomodulatory effects in different stages of the disease and are therefore important as therapeutic targets for schistosomiasis and in vaccine development. A combination of different antigens can provide greater protection, as it possibly stimulates an adequate immune response for an M1 or M2 profile and leads to host resistance; however, this warrants in vitro and in vivo studies.

Diagnostic Accuracy of the Short Physical Performance Battery in Detecting Frailty and Prefrailty in Community-Dwelling Older Adults: Results From the PRO-EVA Study.

BACKGROUND AND PURPOSE: The Short Physical Performance Battery (SPPB) is widely used for older adults since it has a high level of validity, reliability, and responsiveness in measuring function in this population. However, only a few studies of diagnostic accuracy have assessed SPPB capacity in detecting frailty and prefrailty by estimating more detailed measurement properties. Thus, the present study aimed to evaluate the SPPB's diagnostic accuracy in detecting frailty and prefrailty, in addition to identifying cut-off points for walking time and chair stand time. METHODS: This is a cross-sectional study composed of 786 community-dwelling older adults 60 years or older, in which sociodemographic and anthropometric data, frailty phenotype, and total SPPB score, as well as walking time and chair stand time, were assessed. Analysis of a receiver operating characteristic curve was performed to identify the cut-off point, sensitivity, and specificity in the total SPPB score, as well as the walking time and chair stand time for frailty and prefrailty screening. Accuracy and positive and negative predictive values were subsequently calculated. RESULTS AND DISCUSSION: The cut-off points identified for the total SPPB score, walking time, and chair stand time were 9 points or less (accuracy of 72.6%), 5 seconds or less, and 13 seconds or less, respectively, for frailty screening and 11 points or less (accuracy of 58.7%), 4 seconds or less, and 10 seconds or less, respectively, for prefrailty screening. The walking time showed greater frailty discriminatory capacity compared with the chair stand time (effect size = 1.24 vs 0.64; sensitivity = 69% vs 59%; and specificity = 84% vs 75%). CONCLUSIONS: The total SPPB score has good diagnostic accuracy to discriminate between nonfrail and frail older adults using a cut-off point of 9 or less, being better to identify the true negatives (older adults who are not frail). Although the SPPB's diagnostic accuracy measures for detecting prefrailty were low to moderate, this instrument can help in screening prefrail older adults from the cutoff point of 11 or less in the total SPPB score. Identification of prefrail older adults enables implementing early treatment in this target audience and can prevent their advance to frailty.

[Revue systématique des tests cognitifs validés et/ou ayant des normes de référence pour la population canadienne francophone âgée].

Il est essentiel d'utiliser des tests cognitifs ayant été validés et détenant des normes de référence auprès de la population cible, puisque les réalités culturelles et linguistiques différentes entre l'échantillon de validation ou auprès duquel les normes ont été créées et la population cible peuvent affecter les résultats. Cette revue systématique vise à recenser et décrire les tests cognitifs (incluant tests, questionnaires et grilles d'observation) validés et/ou présentant des normes sur la population âgée canadienne francophone. Au total, 46 articles ont été sélectionnés. Cette revue recense 9 tests validés, 20 tests avec normes de référence et 18 tests validés et avec normes, couvrant la majorité des domaines cognitifs (fonctions mnésiques, attentionnelles, exécutives, perceptivo-motrices et langagières), excepté la cognition sociale. La quasi-totalité des échantillons ont été recrutés au Québec. Les tests relevés présentent majoritairement des indices psychométriques satisfaisants et généralement des normes considérant l'âge, le sexe et l'éducation. Cette revue systématique permettra aux cliniciens et chercheurs canadiens en vieillissement d'orienter optimalement leurs choix de tests cognitifs.

New reference values for maximum respiratory pressures in healthy Brazilian children following guidelines recommendations: A regional study.

OBJECTIVE: To determine reference values for maximum static respiratory pressures in healthy children from a Brazilian region, following recommendations of the European Respiratory Society (ERS) and the Brazilian Society of Pneumology and Tisiology (SBPT). METHODS: A cross-sectional observational study was conducted with healthy children (6 to 11 years) of both sexes. The maximum inspiratory and expiratory pressures (PImax and PEmax, respectively) were measured using a digital manometer. Each child performed a minimum of three and a maximum of five maneuvers; three acceptable and reproducible maneuvers were considered for analysis. Minimum time for each maneuver was 1.5 seconds, with a one-second plateau, and one minute of rest between them. A stepwise multiple linear regression analysis was conducted for PImax and PEmax, considering correlations between independent variables: age, weight, and sex. RESULTS: We included 121 children (62 girls [51%]). Boys reached higher values for maximum respiratory pressures than girls. Respiratory pressures increased with age showing moderate effect sizes (PImax: f = 0.36; PEmax: f = 0.30) between the stratified age groups (6-7, 8-9, and 10-11 years). Age and sex were included in the PImax equation (PImax = 24.630 + 7.044 x age (years) + 13.161 x sex; R2 = 0.189). PEmax equations were built considering age for girls and weight for boys [PEmax (girls) = 55.623 + 4.698 x age (years) and PEmax (boys) = 82.617 + 0.612 x weight (kg); R2 = 0.068]. CONCLUSIONS: This study determined new reference equations for maximal respiratory pressures in healthy Brazilian children, following ERS and SBPT recommendations.

Praziquantel: An update on the mechanism of its action against schistosomiasis and new therapeutic perspectives.

Praziquantel (PZQ) is the drug of choice for the treatment of all forms of schistosomiasis, although its mechanisms of action are not completely understood. PZQ acts largely on adult worms. This narrative literature review describes what is known about the mechanisms of action of PZQ against schistosomes from in vitro and in vivo studies and highlights the molecular targets in parasites and immune responses induced in definitive hosts by this drug. Moreover, new therapeutic uses of PZQ are discussed. Studies have demonstrated that in addition to impacting voltage-operated Ca2 + channels, PZQ may interact with other schistosome molecules, such as myosin regulatory light chain, glutathione S-transferase, and transient receptor potential channels. Following PZQ administration, increased T regulatory type 1 (Tr1) cell differentiation and decreased inflammation were observed, indicating that PZQ promotes immunoregulatory pathways. Although PZQ is widely used in mass drug administration schemes, the existence of resistant parasites has not been proven; however, it is a concern that should be constantly investigated in human populations. In addition, we discuss studies that evaluate health applications of PZQ (other than helminth infection), such as its effect in cancer therapy and its adjuvant action in vaccines against viruses.

Histomorphometric analysis of the lung of Swiss mice treated with a fibrinolytic protease.

Fibrinolytic enzymes are considered promising alternative in the treatment of cardiovascular diseases by preventing fibrin clots. A protease from Mucor subtilissimus UCP 1262 was obtained by solid state fermentation and purified by ion exchange chromatography. The purified extract was administered at an acute dose of 2000 mg/mL to evaluate its toxic effects to the lungs of mice. After 14 days of treatment, a histomorphometric study was performed by the type 1 and 2 pneumocyte count and the evaluation of the lung area. As result, the experimental group showed a significant decrease of type 2 pneumocyte and although a decrease in the alveolar area was observed in relation to the control group, no significant pulmonary toxicity, emphysema, and fibrosis characteristics were detected. The in vitro tests suggest possible clinical applications for the enzyme.

Role of TLR9 methylation on its active transcription in apical inflammation.

AIM: To explore the methylation pattern, its role in transcriptional regulation and potential modifiers of methylation of the TLR9 gene in chronic periapical inflammation. METHODOLOGY: In this cross-sectional study, apical lesions of endodontic origin (ALEO, n = 61) and healthy periodontal ligaments (HPL, n = 15) were included. Products from bisulfited and PCR-amplified DNA were analysed for their methylation profiles in the promoter region and at each CpG island. Additionally, TLR9 mRNA levels were quantified by qPCR and bivariate and multiple modelling were performed to better understand the influence of methylation on gene transcription. RESULTS: TLR9 mRNA levels were upregulated in ALEO compared to HPL (p < .001). TLR9 promoter CpG sites and CpG +2086 in the intragenic island 1 were demethylated in ALEO compared to HPL (p < .05). Multivariate analysis, adjusted by smoking and gender, revealed that demethylation of TLR9 promoter sites enhanced transcriptional activity, specifically demethylated CpGs at positions -736 and -683, (p = .02), which are close to CRE binding. Although ALEO reduced the global methylation of the gene promoter and intragenic-island 2 (p < .05) by -42.5 and -9.5 percentage points, respectively, age reduced the global methylation of intragenic-island 3 within the exon 2. CONCLUSIONS: Demethylations of TLR9 promoter CpG sites, along with the intragenic DNA methylation status, were involved in higher transcription in ALEO. Hence, chronic periapical inflammation and ageing modify the methylation status both in the gene promoter and in intragenic CpG islands.

Validación de medidas de resultados informados por los pacientes en ortopedia y traumatología / Validation of patient-reported outcome measures in orthopedics and traumatology

En los últimos años, ha habido un aumento en la aplicación de cuestionarios diseñados para la medición de resultados (o desenlaces) clínicos en la práctica médica. Para aplicar un cuestionario en una población distinta a la cual fue originalmente creado y diseñado, es necesario llevar a cabo un proceso riguroso de adaptación, con una determinada metodología. El objetivo de esta guía metodológica es describir el proceso de traducción, adaptación transcultural y validación de medidas de resultados informados por los pacientes (MRIPs) en Ortopedia y Traumatología.

In recent years, there has been an increase in the use of questionnaires designed to measure outcomes in the medical practice. To use a questionnaire in a population different from the one for which it was originally created and designed, it is necessary to carry out a rigorous adaptation process, with a certain methodology. The objective of the present methodological guide is to describe the process of translation, crosscultural adaptation, and validation of patient-reported outcome measures in Orthopedics and Traumatology